Being rich in phytochemicals, Fenugreek (Trigonella foenum-graecum) has traditionally been used as food, forage and medicinal plant. Fenugreek has a long history of medical uses in Ayurvedic and Chinese medicine, and has been used for numerous indications, including labor induction, aiding digestion, and as a general tonic to improve metabolism and health.
Fenugreek is rich in its chemical constituents. Fenugreek seed contains about 45-60% carbohydrates, mainly mucilaginous fiber (galactomannans); proteins which are high in lysine and tryptophan; fixed oils such as lipids; pyridine-type alkaloids, mainly trigonelline, choline, gentianine, and carpaine; flavonoids such as apigenin, luteolin, orientin, quercetin, vitexin, and isovitexin; free amino acids such as 4-hydroxyisoleucine, arginine, histidine, and lysine; calcium and iron; saponins, like glycosides which yield steroidal sapogenins on hydrolysis (such as diosgenin, yamogenin, tigogenin, neotigogenin); cholesterol and sitosterol; vitamins A, B1, C, and nicotinic acid; volatile oils such as n-alkanes and sesquiterpenes; and sugars such as raffinose, stachyose, sucrose, fructose, mannose, verbascose and xylose. The seeds also contain saponin fenugrin B and coumarin compounds. The seed is also responsible for about 8% of fixed, foul-smelling oil. Several C-glycoside flavones have also been identified in the seeds of fenugreek. These include vitexin, vitexin glycoside, and an arabinoside of orietin (iso-orientin), minor steroidal sapogenins (fenugreekine, smilagenin, sarsasapogenin, yuccagenin), and up to 50% of mucilaginous fiber.
These different chemical constituents have shown diverse therapeutic effects. The component called fenugreekine, a steroidal sapogenin peptide ester has hypoglycemic properties and has shown improved pancreatic function. It helps to delay gastric emptying, slow carbohydrate absorption, and inhibit glucose transport in humans. Trigonelline is suggested to exert hypoglycemic effects in healthy patients without diabetes. The steroidal saponins (diosgenin, yamogenin, tigogenin and neotigogenin) are thought to inhibit cholesterol absorption and synthesis and hence its potential role in arteriosclerosis. It is also used topically to treat inflammation, and to promote postpartum lactation in animals. At present, diosgenin, a steroid sapogenin, is used in the manufacture of birth control pills. Plant phenolics have potential health benefits mainly due to their antioxidant properties such as reactive oxygen species (ROS) scavenging and inhibition, electrophile scavenging and metal chelation. They have also been reported to exhibit pharmacological properties such as antitumor, antiviral, antimicrobial, anti-inflammatory, hypotensive and antioxidant activity.
Thus, fenugreek is researched for different chemical constituents and therapeutic activities. Fenugreek is reported as a cultivated crop in various parts of Europe such as in Austria, France, Germany, Greece, Portugal, Russia, Spain, Switzerland, Turkey and United Kingdom (UK); Northern Africa such as in Egypt, Ethiopia, Kenya, Morocco, Sudan, Tanzania and Tunisia; West and South Asia such as in China, India, Iran, Israel, Japan, Lebanon and Pakistan; North and South America and Australia.
Plant growth and distribution are limited by environmental factors. The environmental aspects that affect plant growth and phyto-chemical distribution are light, temperature, water (humidity), and nutrition. These environmental conditions are different in different geographical locations throughout the world. They have shown prominent effect on plant growth, chemical distribution in terms of quality and quantity of active principles and on genetic diversity as well.
However, due to ever-growing needs of the developing population, there is a need to identify and isolate specific components available in biological sources such as Fenugreek, for several applications.
Oxygen is essential for life. Carbohydrates and fatty acids are the most important fuels for generating ATP in animal cells. Respiration in animal cells depends on oxygen. Electrons from the chemical bonds of the fuel source combine with oxygen and hydrogen ions to form water and carbon dioxide. Cells couple this reaction to the production of ATP. High-energy phosphate in the form of ATP is required for many synthetic and degradative processes within the cell. These include membrane transport, protein synthesis, lipogenesis, and the deacylation-reacylation reactions necessary for phospholipid turnover. The body functioning gets affected because of low levels of oxygen in the blood and air. Ultimately this reduced air and blood flow affects oxygen transportation through the lungs. The impaired levels of oxygen in lungs results in high pressure on arteries and veins leading to scarring of tissues and abnormal arterial and venous blood pressures.
With prolonged or increased depletion of ATP, structural disruption of the protein synthetic apparatus occurs, resulting in detachment of ribosomes from the rough endoplasmic reticulum and dissociation of polysomes into monosomes, with a consequent reduction in protein synthesis. Ultimately, there is irreversible damage to mitochondrial and lysosomal membranes, and the cell undergoes necrosis.
Hypoxia, is a pathological condition in which the body or a region of the body is deprived of an adequate oxygen supply. When oxygen levels are low for a long time, pulmonary arteries constrict and their walls become thickened. This constriction and thickening increase the pressure in the pulmonary arteries. Lung disorders that damage or decrease the amount of lung tissue (for example, emphysema) also decrease the number of blood vessels in the lungs. The decreased number of blood vessels increases pressure in the remaining vessels leading to pulmonary hypertension.
Pulmonary hypertension (PAH) is a rare lung disorder in which the blood pressure in the pulmonary artery rises far above normal levels and may become life threatening. It is characterized by vascular remodelling of the distal pulmonary arterial circulation. The remodelling seen in PAH includes both apoptosis and proliferation of pulmonary vascular endothelial cells, deposition of extracellular matrix proteins, and perivascular inflammation.
Increased pulmonary venous pressure is typically caused by disorders that affect the left side of the heart and raise left chamber pressures, which ultimately lead to elevated pressure in the pulmonary veins. Elevated pulmonary venous pressures can cause acute damage to the alveolar-capillary wall and subsequent edema. Persistently high pressures may eventually lead to irreversible thickening of the walls of the alveolar-capillary membrane, decreasing lung diffusion capacity. In most patients, pulmonary hypertension eventually leads to right ventricular hypertrophy followed by dilation and right ventricular failure. Right ventricular failure limits cardiac output during exertion.
Pulmonary fibrosis (PF) refers to scarring in the lungs. Pulmonary fibrosis is associated with pulmonary vascular remodelling, fostering the development of pulmonary hypertension. It describes a group of lung diseases in which thickening of the walls of the air sacs (called alveoli), caused by scarring the tissue, makes it hard for oxygen to get into the blood. Low oxygen levels (and the stiff scar tissue itself) can cause shortness of breath, particularly when walking and exercising. Pulmonary fibrosis can be caused by an identifiable irritation to the lungs, but in many cases the cause is unknown.
Hypersecretion of airway mucus leads via impairment of the muco-ciliary clearance and bacterial superinfection to respiratory failure. The major components of the mucus matrix forming family of mucins in the airways are MUC5AC and MUC5B. The major components of mucus are large, heavily glycosylated proteins (mucins) that provide airway secretions with their characteristic viscosity, adhesiveness, and elasticity.
Reactive oxygen species (ROS) released from activated neutrophils cause mucin Muc5ac synthesis via transactivation of epidermal growth factor receptor in a human pulmonary mucoepidermoid cell line. Furthermore, neutrophil elastase induces the overexpression of Muc5ac in cultured human bronchial epithelial cells by an oxidant-dependent mechanism. In sinusitis, the mucin formed by Muc5ac genes gets clogged in upper respiratory tract where chick bones and forehead get affected by mucus secretion.
In acute sinusitis, the infection develops quickly (over a few days) and lasts a short time. Many cases of acute sinusitis last a week or so but it is not unusual for it to last 2-3 weeks (that is, longer than most colds). Sometimes it lasts longer. Sinusitis is said to be acute if it lasts from 4-30 days and subacute if it lasts 4-12 weeks. However, in chronic sinusitis, a sinusitis becomes persistent and lasts for longer than 12 weeks.
Current Therapy
Current therapies for PAH include pharmacologic agents that 1) inhibit PDE5, 2) antagonize endothelin, or 3) supplement the prostaglandin pathway with exogenous prostacyclins. These treatments improve longevity and performance of activities of daily life for PAH patients, but do not halt the ongoing cytoproliferative process that inexorably modifies pulmonary vascular architecture, and leads to lung transplant.
Pulmonary rehabilitation—Pulmonary rehabilitation is a structured exercise program for people with chronic lung diseases, including PF and hypoxia, with the goal of restoring a patient's ability to function without extreme breathlessness. Typically, pulmonary rehabilitation will include conditioning; exercise training and breathing exercises; anxiety, stress, and emotional management; nutritional counseling; education; and other components.
Lung Transplantation—Pulmonary fibrosis is now the leading indication for lung transplantation in the United States; in 2013, PF accounted for nearly half of all lung transplants performed. Transplantation can improve both longevity and quality of life in patients who have no other significant health problems.
N-acetylcysteine (NAC): NAC is a naturally occurring anti-oxidant. In the past, it was thought that NAC could help protect the lung from “oxidative injury” that occurs in some forms of PF. In 2014, a clinical trial found that NAC did not have a substantial beneficial impact in Idiopathic Pulmonary Fibrosis (IPF).
Nintedanib (Ofev®): Nintedanib is an anti-fibrotic drug that is approved to treat IPF in the United States. In clinical trials, nintedanib has been shown to slow the decline in lung function in mild-to-moderate IPF. It is taken by mouth twice a day.
These treatments improve longevity and performance of activities of daily life of PF patients, but do not halt scarring of the lung tissues that affect the air sacks and airways leading to ILD or PF and lung transplant.
There are over-the-counter medicines for sinusitis such as Paracetamol and ibuprofen for relieving pain and fever; decongestants and saline nasal sprays or drops for relieving a blocked nose. These drugs provide instant relief but fail to cease the mucous formation in upper respiratory tract. There is need to develop a drug which would able to prevent disease progression by way of stopping mucous formation and clogging of nose leading to sinusitis.
Prior Art:
CN103304605 A discloses a method for preparing a flavonoid glycoside and stilbene glucoside type compound from fenugreek by virtue of a high speed counter-current chromatography (HSCCC) separation technology, so that the separation time is effectively shortened, and the shortcomings of complicated operation, sample dis adsorption loss, low yield, etc., of conventional preparation methods are overcome. According to the method, the technology is simple, the reproducibility is high, the separation efficiency is high; and the obtained monomer content is higher than 96.0 percent. The document revolves around efficient process to obtain glycosides and glucosides.
WO 2009121155 A2 discloses benzopyranone compounds of formula (I) in the manufacture of a medicament that is useful in the treatment of diseases, dysfunctions and disturbances associated with monoamine oxidase, such as depression and diseases related to depression, phobias, attention deficit, drug abuse, behavioral maladjustment, Parkinson's disease, Alzheimer's disease and migraine. In an even more particular embodiment, the disease includes major depression or depressant symptoms that do not respond to conventional treatment with other antidepressants.
CN 103923074 A discloses a method for extracting vitexin and trigonelline from fenugreek. The method comprises various steps of obtaining vitexin and trigonelline containing water extract with the yield of 20%-35%, from a certain quantity of fenugreek seeds and fenugreek leaves. The process results in increased extraction rate of vitexin and trigonelline and also improves the extraction purity of vitexin and trigonelline. Thus, the document mainly focuses on obtaining purer form of trigonelline and vitexin by a patented process.
CN 102920727 A provides a method for preparing extracts rich in vitexin rhamnoside and vitexin glucoside, and relates to the field of herbal extracting of hawthorn leaves. According to the method, vitexin rhamnoside constitutes 30%-55% of the extract while vitexin glucoside constitutes 10%-35% of the extract. The document focuses on obtaining two ingredients of high purity.
Lamia Yacoubi et al (September, 2011) examines fenugreek (Trigonella foenum-graecum Linnaeus), and its phenolylic extract for inhibition of bleomycin induced lung fibrosis in rats. No correlation is found with increasing fibrosis, suggesting that a direct role for inflammation in pulmonary fibrosis is unlikely. The data suggests, in the first hand, that fenugreek's polyphenol has a potent antioxidant activity and therefore has a potent anti-inflammatory activity against bleomycin induced lung fibrosis model in rats, and in the second hand, they confirm that besides inflammation, other factors probably interfere in the pathogenesis of pulmonary fibrosis.
Madhesh Murugesan et al (September, 2011) reveals that administration of fenugreek is more effective in reducing the extent of myocardial damage and significantly counteracted the oxidative stress during isoproterenol induced myocardial infarction in rats.
However, none of the prior arts either alone or in combination teach a composition for use in treating conditions where oxygen levels are reduced less than normal and thereby causing impairment of oxygen in lungs leading to diseases such as hypoxia, pulmonary hypertension, pulmonary fibrosis and sinusitis. There is a need to develop a safe and efficacious regime which would not only cease disease progression but also provide a protection to the organs from being damaged to a stage of transplantation.
Hence, the present disclosure overcomes the various drawbacks observed in the prior art and provides methods for arriving at composition with specific active components from sources such as, but not limited to Fenugreek, and removing all other active principles such as amino acids, alkaloids, saponins, etc. The composition of the present disclosure is effective in managing conditions such as, but not limited to, hypoxia, pulmonary hypertension, pulmonary fibrosis and sinusitis.